2009
DOI: 10.1053/j.gastro.2009.02.065
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Quantification of Epigenetic and Genetic 2nd Hits in CDH1 During Hereditary Diffuse Gastric Cancer Syndrome Progression

Abstract: Background & Aims:Hereditary diffuse gastric cancer (HDGC) families carry CDH1 heterozygous germline mutations; their tumors acquire complete CDH1 inactivation through "2nd-hit" mechanisms. Most frequently, this occurs via promoter hypermethylation (epigenetic modification), and less frequently via CDH1 mutations and loss of heterozygosity (LOH). We quantified the different 2nd hits in CDH1 occurring in neoplastic lesions from HDGC patients. Methods: Samples were collected from 16 primary tumors and 12 metasta… Show more

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Cited by 148 publications
(108 citation statements)
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“…In fact, E-cadherin protein expression, detected by IHC can either be lost or maintained, regardless of CDH1 germline mutation and HDGC tumour stage. Similar observations in HDGC invasive carcinomas have been documented in several studies [52,53]. Thus, IHC analysis of E-cadherin in HDGC lesions (early and advanced) is not a good marker to detect CDH1 gene complete inactivation or to predict whether an early lesion will evolve or not to invasive cancer.…”
Section: New Insights In Morphological Immunohistochemical and Genetsupporting
confidence: 72%
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“…In fact, E-cadherin protein expression, detected by IHC can either be lost or maintained, regardless of CDH1 germline mutation and HDGC tumour stage. Similar observations in HDGC invasive carcinomas have been documented in several studies [52,53]. Thus, IHC analysis of E-cadherin in HDGC lesions (early and advanced) is not a good marker to detect CDH1 gene complete inactivation or to predict whether an early lesion will evolve or not to invasive cancer.…”
Section: New Insights In Morphological Immunohistochemical and Genetsupporting
confidence: 72%
“…In fact, 50% of primary GC displayed CDH1 epigenetic modifications as a second-hit, whereas in GC metastases the most common second-hit was loss of heterozygosity. Different neoplastic lesions from the same patient frequently displayed different types of second-hits and different types of second-hits were also found within the same tumour sample [50,52,53]. These results demonstrated substantial heterogeneity in the mechanisms that can act as CDH1 second-hits in a single patient.…”
Section: Inactivation Of the 2nd Cdh1 Allelementioning
confidence: 78%
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